Abstract The growth in procedure volume at Ambulatory Surgical Centers (ASCs) has coincided with the growth in surgery performed on the elderly and on more vulnerable patients with multimorbidity (MM). This proposal aims to examine outcomes of patients with multimorbidity who were treated either at an ASC or at a hospital setting, including hospital outpatient (HOPD) and inpatient settings, in order to provide guidance as to where MM patients should receive their care. Understanding the answer to this question will greatly inform policy aimed at protecting patients with MM, and provide guidance to patients and their surgeons about what characteristics of the operative setting and the patient are important for ensuring better outcomes. Because the decision to operate on a patient with MM must weigh the increased operative risks in the MM population, and because the choice of operative setting (ASC versus hospital) is critical to this calculation, we will present specific approaches to studying this setting question, we aim to closely define patient characteristics through the use of multivariate matching. AIM 1 will define the pattern of surgery performed at ASCs, hospital outpatient (HOPD) and inpatient locations in elderly patients with and without MM using the new Virtual Research Data Center at CMS, allowing us to examine the entire country's data from 2008 to 2017. Using our new approach to defining MM for general surgery and orthopedic surgery, and exploring ophthalmologic and diagnostic procedures, we will be able to describe differences in setting (including by the characteristics of ASCs, hospitals, and physicians) for patients undergoing surgery, with and without MM, between ASC and hospital settings. AIM 2 will examine differences in outcomes across initial ASC and initial HOPD settings for MM cases through the use of multivariate matching. Hypothesis 2.1 will explore differences in outcomes for matched MM patients between ASC and HOPD settings. Hypothesis 2.2 will explore differences in outcomes between matched MM and non-MM patients by specified ASC settings (exploring differential outcomes in MM patients by the characteristics of the ASC, using ownership, volume, location in relation to hospitals, anesthesia staffing, physician characteristics, and alignment of ASC case-mix to the individual index case). Hypothesis 2.3 will examine outcome differences between specific MM patient subgroups at the ASC versus HOPD setting. AIM 3 will examine differences in outcomes across ASC and HOPD settings for the non-MM cases using hypotheses parallel to AIM 2. Through this research, we aim to identify procedures and types of MM patients that should be encouraged to or discouraged from having surgery in specific settings in order to improve expected outcomes for this especially vulnerable population. Furthermore, using a similar analytic approach, we will also learn about differential outcomes across settings in the non-MM population. In the end, our study results should be directly helpful in informing the decision regarding where to undergo surgery for patients in the Medicare population.